The long-term objective of the proposed research is to evaluate the role of cardiac mechanisms in the etiology of sudden death in the Sudden Infant Death Syndrome (SIDS). Thus this project is directly related to a problem in infant survival and health. The specific aims of the proposed research are designed to test the hypothesis that a developmental anomaly in cardiac innervation could reduce ventricular electrical stability and favor the onset of sudden cardiac death. The research design and surgical methods have been worked out in the previous grant period; newborn swine with surgically induced imbalance in cardiac autonomic innervation will be continuously monitored (24 hrs.) throughout eight postnatal weeks. Those surviving and similarly surgically prepared littermates will be tested (at ages 2,4,6,8 wks) for cardiovascular responses to: (i) hypoxia, (ii) hypercapnia, (iii) stimulation of cardiopulmonary receptors, and (iv) alterations in baroreceptor afferent inputs. Results obtained from study of these possible precipitating factors should reveal the increased susceptibility of the neonate at risk for sudden death. Sleep is the predominant behavioral state of the neonate and ontogeny of EEG sleep in neonates can be monitored by serial EEG recordings. We plan to examine ECG recordings as a function of state determined by VCR tapes of behavior, diaphragmatic EMG and EEG, and correlate these variables against both age and type of denervation. Nonlinear analysis of heart rate variability in infants has revealed an increase in complexity with maturation and our own results included similar findings in piglets. This grant proposal would pursue these findings and the effects of selected cardiac denervation on this complexity, correlating results with sudden death in denervated piglets. Such studies should confirm our working hypothesis regarding the importance of cardiac innervation in the etiology of sudden death in infants. We are, therefore, postulating an abnormality at the effector level, i.e., at the cardiac level, specifically: maturation of the normal innervation of the heart and its reflex control.